The recent work of Gorman and Marmor (1970, a.b) and Thomas 1972 a,b) has established that the electrogenic sodium-potassium coupled membrane pump is the major, although not necessarily the only source of the metabolic contribution to the membrane potential (Baker et al., 1969a). One of the major unanswered questions is whether electrogenicity is a coincidental property of the cation pump of an electrophysiologically significant component of membrane function. A system which contributes up to 40 percent of the resting membrane potential of some cells may be expected to have inffuence on excitable membrane electrical properties. The electrogenic pump of the crayfish medial giant axon is modulated by external ions and membrane potential such that a perturbation of normal steady-state conditions was attenuated by a "negative-feedback" system (Lieberman and Lundegard, 1973). The mechanism of fine modulation of the electrogenicity of the cation pump system will be studied from the following approaches: (1) Electrophysiological--the role of external and internal environment (ions, membrane potential, physiologic and pharmacologic chemical agents) on the nature and contribution of the pump to membrane potential, critical firing level, delayed rectification, and accommodation. (2) Biochemical--the effects of chemical agents on the Na-K activated ATPase of axon membrane fragments and a study of metabolic modulation of ATPase activity by other membrane related enzymatic systems (adenylcyclase, phosphodiesterase, acetylcholinesterase). (3) Application of these results to the understanding of the mechaism of pacemaker potentials of neurons, cardiac and smooth muscle pacemaker cells (Carpenter, 1960; Job, 1969) and to the plteau and repolarization phase of the ventricular cardiac muscle cell action potential (Hollander and Nosek, 1963).